Human t-Complex Protein 11 (TCP11), a Testis-Specific Gene Product, Is a Potential Determinant of the Sperm Morphology
Human t-Complex Protein 11 (TCP11), a Testis-Specific Gene Product, Is a Potential Determinant of the Sperm Morphology
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人类 T 复合体蛋白 11 (TCP11) 是一种睾丸特异性基因产物，是精子形态的潜在决定因素
DOI：
10.1620/tjem.224.111
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发表时间：
2011-06-01
影响因子：
2.2
通讯作者：
Ma, Yongxin
中科院分区：
文献类型：
--
作者：
Liu, Yanyan;Jiang, Min;Ma, Yongxin
受精促进肽（FPP）在能化和顶体反应中起重要作用。小鼠t-复合物蛋白11 （Tcp11）基因编码FPP受体，在受精过程中起重要作用。我们鉴定了其人类同源基因TCP11的三个备选剪接产物，分别命名为TCP11a、TCP11b和TCP11c。他们的睾丸特异性表达已被注意到，这表明TCP11可能在精子发生和精子功能中起重要作用。为了探讨TCP11的功能，我们研究了TCP11在精子中的表达、亚细胞定位和结合蛋白。RT-PCR分析显示TCP11的所有亚型都存在于人类睾丸和精子中。然而，通过western blot分析，我们只能检测到56-kDa蛋白的表达，代表TCP11a和TCP11c，而不能检测到TCP11b。此外，在含有超过15%的卷曲精子的精子样品中，56-kDa TCP11蛋白的表达水平比正常形态精子样品中的表达水平低约三倍。蜷曲的精子，显示出尾巴的蜷曲或弯曲，与不孕症有关。此外，以TCP11a全长为诱饵，分离出多个TCP11a结合蛋白。其中，我们重点研究了外密纤维1 (outer dense fiber 1, ODF1)，这是精子尾部外密纤维的一种成分，因为外密纤维有助于精子尾部不同的形态和功能。精细胞提取物的共免疫沉淀实验证实TCP11蛋白与ODF1相互作用。这些结果提示TCP11可能与精子尾部形态和运动有关。
Fertilization promoting peptid (FPP) is essential for capacitation and acrosome reaction. The mouse t-complex protein 11 (Tcp11) gene, which encodes the receptor of FPP, plays an important role in fertilization. We had identified three alternative splicing products of its human homologous gene, TCP11, nominated as TCP11a, TCP11b and TCP11c. Their testis-specific expression had been noted, suggesting that TCP11 may play an important role in spermatogenesis and sperm function. In order to explore the function of TCP11, we investigated its expression, subcellular location and binding protein in the sperm. RT-PCR assay shows that all isoforms of TCP11 are present in both human testis and sperm. However, we could only detect the expression of 56-kDa protein, representing TCP11a and TCP11c, but not TCP11b, by western blot analysis. Furthermore, the expression level of 56-kDa TCP11 protein was lower by about threefold in sperm samples containing over 15% of coiled sperms than the level in sperm samples with normal morphology. The coiled sperm, which shows a coiling or bending back of the tail on itself, is associated with infertility. In addition, several TCP11a-binding proteins were isolated using full-length TCP11a as bait. Among them, we focused on outer dense fiber 1 (ODF1), a component of sperm tail outer dense fibers, because outer dense fibers contribute to the distinct morphology and the function of sperm tail. Co-immunoprecipitation assays of sperm cell extracts confirmed that TCP11 protein interacted with ODF1. These results suggest that TCP11 may be responsible for the sperm tail morphology and motility.